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Item Antimicrobial Effects of Novel Triple Antibiotic Paste-Mimic Scaffolds on Actinomyces naeslundii Biofilm(Elsevier, 2015-08) Albuquerque, Maria T.P.; Ryan, Stuart J.; Münchow, Eliseu A.; Kamocka, Maria M.; Gregory, Richard L.; Valera, Marcia C.; Bottino, Marco C.; Department of Medicine, IU School of MedicineINTRODUCTION: Actinomyces naeslundii has been recovered from traumatized permanent teeth diagnosed with necrotic pulps. In this work, a triple antibiotic paste (TAP)-mimic scaffold is proposed as a drug-delivery strategy to eliminate A. naeslundii dentin biofilm. METHODS: Metronidazole, ciprofloxacin, and minocycline were added to a polydioxanone (PDS) polymer solution and spun into fibrous scaffolds. Fiber morphology, mechanical properties, and drug release were investigated by using scanning electron microscopy, microtensile testing, and high-performance liquid chromatography, respectively. Human dentin specimens (4 × 4 × 1 mm(3), n = 4/group) were inoculated with A. naeslundii (ATCC 43146) for 7 days for biofilm formation. The infected dentin specimens were exposed to TAP-mimic scaffolds, TAP solution (positive control), and pure PDS (drug-free scaffold). Dentin infected (7-day biofilm) specimens were used for comparison (negative control). Confocal laser scanning microscopy was done to determine bacterial viability. RESULTS: Scaffolds displayed a submicron mean fiber diameter (PDS = 689 ± 312 nm and TAP-mimic = 718 ± 125 nm). Overall, TAP-mimic scaffolds showed significantly (P ≤ .040) lower mechanical properties than PDS. Within the first 24 hours, a burst release for all drugs was seen. A sustained maintenance of metronidazole and ciprofloxacin was observed over 4 weeks, but not for minocycline. Confocal laser scanning microscopy demonstrated complete elimination of all viable bacteria exposed to the TAP solution. Meanwhile, TAP-mimic scaffolds led to a significant (P < .05) reduction in the percentage of viable bacteria compared with the negative control and PDS. CONCLUSIONS: Our findings suggest that TAP-mimic scaffolds hold significant potential in the eradication/elimination of bacterial biofilm, a critical step in regenerative endodontics.Item The antimicrobial efficacy of innovative 3D triple antibiotic paste-mimic tubular scaffold against actinomyces naeslundii(2015) Azabi, Asma Abulqasem; Bottino, Marco C.; Gregory, Richard L.; Spolnik, Kenneth J.; Cook, Norman Blaine, 1954-; Chu, Tien-Min GabrielBackground: Root canal disinfection is an essential requirement for the success of regenerative endodontics. Currently, the so-called triple antibiotic paste (TAP) is considered the standard of care. Notwithstanding the good antimicrobial capacity, the high concentration of TAP has shown significant toxicity to human cells, especially dental pulp stem cells. A novel drug release system, i.e., a triple antibiotic paste-mimic electrospun scaffold containing low concentrations of the antibiotics present in the TAP, has emerged as an effective and reliable alternative to fight root canal infections without potential toxic effects on dental stem cells, which are an integral part of the regenerative treatment. Objectives: The aim of this study was to determine the antimicrobial efficacy of an innovative three-dimensional (3D) triple antibiotic paste-mimic tubular scaffold against Actinomyces naeslundii biofilm formed inside human root canal dentinal tubules. Materials and methods: Pure polydioxanone (PDS) polymer solution and PDS loaded with metronidazole, ciprofloxacin and minocycline (35 wt.% of each antibiotic, 3D-TAP-mimic scaffold) were spun into 3D fibrous scaffolds. A. naeslundii (ATCC 43146) was centrifuged to induce biofilm formation inside human root canal dentinal tubules using a dentin slice model (1 mm thickness and 2.5 mm canal diameter). The infected dentin slices were exposed to the 3D-TAP-mimic scaffold, TAP solution (50 mg/mL of each antibiotic), and antibiotic-free PDS. Biofilm elimination was quantitatively and qualitatively analyzed by confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM), respectively. Results: A dense penetration of A. naeslundii biofilm was observed by CLSM throughout the dentinal tubules. 3D-TAP-mimic scaffold significantly reduced the percentage of viable bacteria compared with PDS (p <.05). TAP solution completely eliminated viable bacteria without differing from 3D-TAP-mimic scaffolds. SEM images showed results similar to CLSM. Conclusion: Collectively, the proposed tubular 3D-TAP-mimic scaffold holds significant clinical potential for root canal disinfection strategy prior to regenerative endodontics.Item Antimicrobial Efficacy of Triple Antibiotic-Eluting Polymer Nanofibers against Multispecies Biofilm(Elsevier, 2017-09) Albuquerque, Maria T.P.; Nagata, Juliana; Bottino, Marco C.; Biomedical Sciences and Comprehensive Care, School of DentistryThe elimination of microbial flora in cases of immature permanent teeth with necrotic pulp is both key and a challenging goal for the long-term success of regenerative therapy. Recent research has focused on the development of cell-friendly intracanal drug delivery systems. This in vitro study aimed to investigate the antimicrobial action of 3-dimensional (3D) tubular-shaped triple antibiotic-eluting nanofibrous constructs against a multispecies biofilm on human dentin. Polydioxanone polymer solutions, antibiotic-free or incorporated with metronidazole, ciprofloxacin, and minocycline, were electrospun into 3D tubular-shaped constructs. A multispecies biofilm consisting of Actinomyces naeslundii, Streptococcus sanguinis, and Enterococcus faecalis was forced inside the dentinal tubules via centrifugation in a dentin slice in vitro model. The infected specimens were exposed to 2 experimental groups (ie, 3D tubular-shaped triple antibiotic-eluting constructs and triple antibiotic paste [TAP]) and 2 control groups (7-day biofilm untreated and antibiotic-free 3D tubular-shaped constructs). Biofilm elimination was quantitatively analyzed with confocal laser scanning microscopy. Confocal laser scanning microscopic (CLSM) analysis showed a dense population of viable (green) bacteria adhered to dentin and penetrated into the dentinal tubules. Upon 3D tubular-shaped triple antibiotic-eluting nanofibrous construct exposure, nearly complete elimination of viable bacteria on the dentin surface and inside the dentinal tubules was shown in the CLSM images, which was similar (P < .05) to the bacterial death promoted by the TAP group but significantly greater when compared with both the antibiotic-free 3D tubular-shaped constructs and the control (saline). The proposed 3D tubular-shaped antibiotic-eluting construct showed pronounced antimicrobial effects against the multispecies biofilm tested and therefore holds significant clinical potential as a disinfection strategy before regenerative endodontics.Item Bioactivity of Dental Restorative Materials: FDI Policy Statement(Elsevier, 2023) Schmalz, Gottfried; Hickel, Reinhard; Price, Richard Bengt; Platt, Jeffrey A.; Biomedical Sciences and Comprehensive Care, School of DentistryThe term bioactivity is being increasingly used in medicine and dentistry. Due to its positive connotation, it is frequently utilised for advertising dental restorative materials. However, there is confusion about what the term means, and concerns have been raised about its potential overuse. Therefore, FDI decided to publish a Policy Statement about the bioactivity of dental restorative materials to clarify the term and provide some caveats for its use in advertising. Background information for this Policy Statement was taken from the current literature, mainly from the PubMed database and the internet. Bioactive restorative materials should have beneficial/desired effects. These effects should be local, intended, and nontoxic and should not interfere with a material's principal purpose, namely dental tissue replacement. Three mechanisms for the bioactivity of such materials have been identified: purely biological, mixed biological/chemical, or strictly chemical. Therefore, when the term bioactivity is used in an advertisement or in a description of a dental restorative material, scientific evidence (in vitro or in situ, and preferably in clinical studies) should be provided describing the mechanism of action, the duration of the effect (especially for materials releasing antibacterial substances), and the lack of significant adverse biological side effects (including the development and spread of antimicrobial resistance). Finally, it should be documented that the prime purpose, for instance, to be used to rebuild the form and function of lost tooth substance or lost teeth, is not impaired, as demonstrated by data from in vitro and clinical studies. The use of the term bioactive dental restorative material in material advertisement/information should be restricted to materials that fulfil all the requirements as described in the FDI Policy Statement.